Nmr and molecular dynamics study of four carbocyclic muramyl dipeptide analogues

We have performed a conformational analysis of the carbocyclic muramyl dipeptide analogues (1′R, 2′R)- and (1′S, 2′S)-N-2-(2′-acetamidocyclohexyIoxy)acetyl]-L Ala-D -iGln (-D -Glu) utilizing ¹H-nmr spectroscopy and nuclear Overhauser effect restrained molecular dynamics. Intramolecular H bonding for all four diastereoisomers is suggested by the Ala-NH temperature coefficients. Distance restraints were obtained by NOE spectroscopy and rotating frame NOE spectroscopy experiments. Structures with low potential energy and high agreement with NOE data were sought by restrained molecular dynamics. The ring configuration was found to induce conformational preferences. The β-like turn characterized by the intramolecular C₁₀ H-bond Ala-NH-acetamido-CO is preferred with the (1′S, 2′S), but appears to be less stable with (1′R, 2′R), diastereoisomers. Calculations show the double β-turn proposed for muramyl dipeptide S. Fermandjian, B. Perly, M. Level, and P. Lefrancier (1987) Carbohydrate Research, Vol. 162, pp. 23–32] to have higher potential energy. © 1993 John Wiley & Sons, Inc.